Social adversity, both in early life and adulthood, can have major and long-lasting impacts on human health. Low social status and social isolation in early life have been linked to changes in the immune response and elevated rates of cardiovascular disease later in life, even when status differences are erased. At the same time, social adversity in adulthood - unconnected to any early life experience - has well-documented effects on mortality risk. Thus, traits that are influenced by social conditions early in life reman, at least to some degree, responsive to later social environments. However, the mechanisms that mediate these dual properties-long-term stability coupled with the potential for plasticity an change-remain poorly understood. In particular, we do not understand the molecular mechanisms that translate social experiences across the life course into physiological changes that affect health and disease risk. The goal of the proposed work is to leverage a powerful animal model for social adversity in humans-dominance rank in nonhuman primates-to investigate the relative contributions of early life and adult social status to variation in DNA methylation levels. DNA methylation is an epigenetic mechanism that may serve as an important link between social environment, physiology, and health. However, while this relationship has been investigated in detail for a handful of loci, we do not yet understand its importance genome-wide, or the degree to which changes in DNA methylation in response to the social environment depend on the timing of exposure. Intensively studied primate populations can serve as important models for these questions because known individuals are directly observed from conception to death, and social environmental effects are not confounded by other predictors of health, such as access to health care, diet, or smoking. This application takes advantage of one such population, the well-studied Amboseli baboon population of Kenya, to assess whether and how the relationship between social adversity and DNA methylation changes over the life course. Specifically, we propose to investigate the contribution of social status, in both early life and in adulthood, to patterns of genome-wide DNA methylation in blood. We will investigate targets of DNA methylation that are associated with early life social status, adult social status, or both;if both, we will further test whether these effects act independently. Because variation in DNA methylation levels does not always affect variation in other traits, we will also complement these data with data on gene expression levels from the same individuals, obtained during the same blood draw. The gene expression data will reveal the degree to which DNA methylation patterns that are sensitive to social status also influence downstream gene expression levels. Together, our results will help establish not only whether social status influences DNA methylation, but also the role of different stages of the life course in this relationship and the likelihood that epigenetic mechanisms explain broader relationships between social adversity and health.

Public Health Relevance

The social environment can have profound effects on health and wellbeing. However, we do not yet understand the relative importance of social conditions at different stages of the life course, or the mechanisms underlying their effects. We propose to use a powerful animal model-an intensively studied natural population of baboons in Kenya- to examine how an important epigenetic mechanism, DNA methylation, is affected by social status both early in life and in adulthood. This work will lay a strong foundation for understanding the relationship between epigenetics, social adversity, and human health.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG049936-01
Application #
8768775
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gerald, Melissa S
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
Social Sciences
Type
Schools of Arts and Sciences
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705